Stabilities of nucleic acid conformations and ligand-nucleic acid complexes are strongly dependent on salt (e.g. NaCl, MgCl2) concentrations because of the importance of coulombic interactions in these poly- or oligoelectrolyte systems. Since the cell is a concentrated polyelectrolyte environment in which the concentrations of salt and polyamines (oligocations) are variable, studies of coulombic effects of salt concentration on stability of nucleic acid conformations and complexes are of biological as well as biochemical relevance. Although cellular nucleic acids are polyanions, many biochemical studies on the stability of their conformations and complexes use short oligonucleotides (oligoanions) and oligocationic ligands as model systems. A systematic thermodynamic characterization of the coloumbic properties of oligomeric and polymeric nucleic acids and their complexes will allow comparison of behavior in the test tube vs. the cell, provide quantitative insight into coulombic contributions to stability, and serve as models for oligo and polysaccharides and other structurally less characterized biopolyelectrolytes. Our specific aims are to quantify the molecular and thermodynamic basis of the large differences between oligo- and polyelectrolyte nucleic acids with regard to the coulombic contribution to stability of conformations and complexes as a function of salt concentration. Our experimental and computational studies will examine homologous series of oligonucleotides and cationic oligopeptides with variable number of charges lZl. We will characterize the "context-dependence" of the coulombic contribution to stability which arises from coulombic end effects. Examples (observed or predicted) include the quantitatively different effects of salt concentration on stability of i) hairpin vs. two-stranded helices of the same number of base pairs, ii) oligo-oligo vs. oligo-polymer helices of the same number of base pairs and iii) oligocation (or protein)complexes with oligo vs. polyanionic DNA, or at the end vs. in the interior of a DNA molecule. Rigorous Monte Carlo computer simulations and 23Na NMR and osmotic pressure measurements will be used to characterize salt-nucleic acid interactions as a function of salt concentration. Scanning and titration calorimetry and spectroscopic methods will be used to characterize coulombic end effects on stability of nucleic acid conformations and complexes as functions of lZl and salt concentration. Thermodynamic transformations will be used to relate MC computational results and experimental results. Heat capacity changes (deltaCPdegrees) for nucleic acid processes will be determined by titration and/or scanning calorimetry, and interpreted in terms of the contribution of the hydrophobic effect to stability of nucleic acid helices and ligand- nucleic acid complexes.